(1) Field of the Invention
The present invention relates to adhesives for percutaneous absorption adhesive compositions for percutaneous absorption and preparations for percutaneous absorption, used in order to administer a drug through the skin continuously over along period.
(2) Description of the Related Art
In recent years various preparations such as patches and tapes for external use attached to the surface of the skin have been developed as preparations for percutaneous absorption in order to administer drugs through the surface of the skin. In this kind of adhesive preparation, the role of the adhesive is extremely important and the adhesive is required to adhere to the skin, to permit stable sustained drug release and to show little irritation to the skin. In order for these preparations for percutaneous absorption to show these characteristics, an adhesive which permits stable drug release over a long period (3 days to a week) after attachment is important.
However, the adhesives for preparations for percutaneous absorption proposed in the prior art cannot considered suitable for long term continuous drug administration.
For example, JP2-203048 A proposes an adhesive for external use which uses a copolymer which is a copolymer formed from an alkyl ester of acrylic acid or methacrylic acid at 40-80 wt %, an ethylenic unsaturated monomer containing a hydroxyl group at 10-50 wt % and an ethylenic unsaturated monomer containing a carboxyl group at 1-10 wt %, which has a glass transition temperature. (Tg) of 250K or less and a gel content after drying of 25 wt % or more. This adhesive for medical use has the disadvantage that the content in the copolymer of ethylenic unsaturated monomers having an alkoxy group is low, and therefore the saturation solubility of drugs and absorption promoters is low.
JP4-150865 A proposes an adhesive which includes a crosslinked copolymer of 99-99.9 wt % of a mixture of an acrylic acid alkyl ester and alkoxyalkyl acrylate in which the proportion of the alkoxyalkyl ester of acrylic acid at 50 wt % or less, together with a monomer containing a carboxyl group and/or hydroxyl group at 0.1-1 wt %. This adhesive is based on a (meth)acrylic acid ester, and like JP 2-232048 A above it has the drawback that the saturation solubility of drugs and absorption promoters is low.
JP 4-272754 A discloses adhesives for medical use which include more than 50% of a monomer derived from an alkoxyalkyl ester of acrylic acid which gives a homopolymer with a Tg of −35° C.; however, in this invention. Methoxyethyl acrylate is positively excluded as being unsuitable. Moreover, as the comparison examples presented below will show drugs and absorption promoters have a plasticizing effect on these adhesives, and they have the drawback that the cohesion of the adhesive composition is lowered and there are considerable adhesive residues left on the skin.
Since impregnation of drugs into the adhesive at high concentration and long-term sustained high release are important in the development of preparations for percutaneous absorption, various techniques have been proposed with the object of long-term sustained high drug release. For example, JP 5-246752 A proposes adhesives for percutaneous absorption comprising a mixture of an acrylate adhesive or silicone adhesive and Poly(Vinylpyrrolidone) as adhesives allowing the stable presence of drugs in the supersaturated state without crystallization. However, this technique is proposed in order to maintain a thermodynamically unstable state of supersaturation for a long time, and there is a considerable risk of recrystallization of the drug, limiting the efficacy thereof. Similarly; JP 6-75600 A proposes preparations for percutaneous absorption impregnated with tulobuterol in the dissolved state and the crystalline state. These preparations also have the drawback that in many cases, crystallization of the drug causes lowered adhesion of the adhesive preparation.